Background

In some patients with atrial fibrillation (AF) and renal dysfunction who are on anticoagulant treatment, worsening renal function (WRF) is observed over time [1-4]. It is unclear whether WRF during anticoagulation has an impact on the clinical outcomes of these patients, compared to stable renal function (SRF). Moreover, it is not known whether in AF patients with WRF, clinical outcomes differ according to the type of anticoagulation therapy (new oral anticoagulants vs. warfarin).

In the ROCKET AF trial, rivaroxaban was compared with warfarin for the prevention of stroke and systemic embolism in 14 264 patients with AF [5,6]. Patients with moderate renal dysfunction at baseline (creatinine clearance [CrCl]: 30 – 49 mL/min), received a reduced dose of rivaroxaban
(15 mg once daily), and the study medication was discontinued if CrCl dropped below 25 mL/min.
In this analysis of the ROCKET AF study, it was evaluated whether the primary efficacy and safety endpoints differed between WRF (reduction in CrCl>20% while on treatment) patients taking rivaroxaban compared with those on warfarin.

Main results

The rate of patients with WRF did not differ between those randomised to rivaroxaban (26%, n=1632/6253) and those on warfarin (27%, n=1688/6359, P=0.09).

The primary efficacy outcome (stroke/non-CNS embolism) was seen at a similar rate in those with WRF and SRF (HR: 1.25, 95%CI: 0.89-1.75, P=0.19).

No statistically significant difference between WRF and SRF patients was seen for the primary safety end point of ISTH major or NMCR bleeding (adjusted HR: 1.05; 95% CI: 0.90–1.21; P=0.55) and gastrointestinal bleeding (adjusted HR: 1.18; 95% CI: 0.78–1.77; P=0.44).

Fewer stroke or systemic embolism events were seen in patients with WRF on rivaroxaban vs. warfarin (1.54 vs. 3.25 events per 100 patient-years (PY)), a difference that was not seen in SRF patients (1.80 vs. 1.83 events per 100 PY, P=0.050 for interaction).

Haemoglobin decrease ≥2 g/dL was more often seen in WRF patients on rivaroxaban, as compared with those on warfarin (3.56 vs. 1.85 events per 100 PY), while no difference was seen between treatments in SRF patients (2.22 vs. 2.19 events per 100 PY, P=0.047 for interaction).

WRF patients randomised to rivaroxaban had a greater incidence of gastrointestinal bleeding that was not seen in SRF patients (3.21 vs. 1.28 events per 100 PY for rivaroxaban vs warfarin; P=0.02 for interaction).

Conclusion

In AF patients with on-treatment worsening renal function, rivaroxaban was associated with a lower rate of the primary end point of stroke and systemic embolism compared with warfarin without an increase in the composite bleeding end point. In patients with WRF, differences in the rates of certain clinical events were seen between treatment arms, which were not evident in patients with SRF.